2021Clinical & Translational ImmunologyOpen access

A novel method to standardise serum IgA measurements shows an increased prevalence of IgA deficiency in young children with recurrent respiratory tract infections

Mischa H. Koenen, Madeleen Bosma, Udo A Roorda, Fabiënne MY Wopereis, Anja Roos, Erhard van der Vries, Debby Bogaert, Elisabeth A. M. Sanders, Marianne Boes, Jojanneke Heidema, Joris M. van Montfrans, Walter Balemans, Thijs C. van Holten, Lilly M. Verhagen

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Abstract

Abstract Objectives While physicians are often confronted with immunoglobulin A (IgA) deficiency in children with recurrent infections, the clinical relevance of this finding is unclear. Large‐scale studies examining the significance of IgA deficiency in children are hampered by differences in techniques for measuring IgA and the physiological increase of IgA with age. Both result in a variety of reference values used for diagnosing IgA deficiency. We propose a new laboratory‐independent method to accurately compare IgA measurements in children of varying ages. Methods We present a method to standardise IgA values for age and laboratory differences. We applied this method to a multicentre case–control study of children under the age of seven suffering from recurrent respiratory tract infections (rRTI, cases) and children who had IgA measured as part of coeliac disease screening (controls). We defined IgA deficiency as serum IgA measurements < 2.5% for age‐specific reference values. Results We developed reference values for IgA for seven age groups and five different laboratory assays. Using these reference values, IgA measurements from 417 cases and 224 controls were standardised to compare groups. In children aged 2 years and older, IgA deficiency was observed in 2.9% (7/242) of cases and 0% (0/189) of controls (P = 0.02). Conclusion We present a method to compare IgA values in cohorts that vary in age and laboratory assay. This way, we showed that IgA deficiency was more prevalent in children with rRTI compared with controls. This implicates that IgA deficiency may be a clinically relevant condition, even in young children.

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Abstract Objectives While physicians are often confronted with immunoglobulin A (IgA) deficiency in children with recurrent infections, the clinical relevance of this finding is unclear. Large‐scale studies examining the significance of IgA deficiency in children are hampered by differences in techniques for measuring IgA and the physiological increase of IgA with age. Both result in a variety of reference values used for diagnosing IgA deficiency. We propose a new laboratory‐independent method to accurately compare IgA measurements in children of varying ages. Methods We present a method to standardise IgA values for age and laboratory differences. We applied this method to a multicentre case–control study of children under the age of seven suffering from recurrent respiratory tract infections (rRTI, cases) and children who had IgA measured as part of coeliac disease screening (controls). We defined IgA deficiency as serum IgA measurements < 2.5% for age‐specific reference values. Results We developed reference values for IgA for seven age groups and five different laboratory assays. Using these reference values, IgA measurements from 417 cases and 224 controls were standardised to compare groups. In children aged 2 years and older, IgA deficiency was observed in 2.9% (7/242) of cases and 0% (0/189) of controls (P = 0.02). Conclusion We present a method to compare IgA values in cohorts that vary in age and laboratory assay. This way, we showed that IgA deficiency was more prevalent in children with rRTI compared with controls. This implicates that IgA deficiency may be a clinically relevant condition, even in young children.

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Available abstract

Abstract Objectives While physicians are often confronted with immunoglobulin A (IgA) deficiency in children with recurrent infections, the clinical relevance of this finding is unclear. Large‐scale studies examining the significance of IgA deficiency in children are hampered by differences in techniques for measuring IgA and the physiological increase of IgA with age. Both result in a variety of reference values used for diagnosing IgA deficiency. We propose a new laboratory‐independent method to accurately compare IgA measurements in children of varying ages. Methods We present a method to standardise IgA values for age and laboratory differences. We applied this method to a multicentre case–control study of children under the age of seven suffering from recurrent respiratory tract infections (rRTI, cases) and children who had IgA measured as part of coeliac disease screening (controls). We defined IgA deficiency as serum IgA measurements < 2.5% for age‐specific reference values. Results We developed reference values for IgA for seven age groups and five different laboratory assays. Using these reference values, IgA measurements from 417 cases and 224 controls were standardised to compare groups. In children aged 2 years and older, IgA deficiency was observed in 2.9% (7/242) of cases and 0% (0/189) of controls (P = 0.02). Conclusion We present a method to compare IgA values in cohorts that vary in age and laboratory assay. This way, we showed that IgA deficiency was more prevalent in children with rRTI compared with controls. This implicates that IgA deficiency may be a clinically relevant condition, even in young children.

Key concepts: IgA deficiency, Immunoglobulin A, Medicine, Selective IgA deficiency, Coeliac disease, Immunology, Clinical significance, Antibody

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